Autoantibodies directed against the insulin receptor are an uncommon cause of severe insulin resistant diabetes mellitus. Antibodies and insulin compete with each other for binding. Both insulin and antibody induce negatively cooperative site-site interactions. Concanavalin A which has previously shown to inhibit negative cooperativity induced by insulin also inhibits the accelerated dissociation of prebound antibody. The spontaneous dissociation of both prebound insulin and antibody was pH dependent, although that of insulin was more sensitive. Thus this anti-receptor autoantibody possesses extraordinary insulin-like characteristics: competing with insulin for the receptor, stimulating receptor mediated responses and inducing negative cooperativity. BIBLIOGRAPHIC REFERENCE: Jarrett, D.B., Roth, J., Kahn, C.R., Flier. J.S.: Direct Method for Detection and characterization of cell surface receptors for insulin by means of 125I-labeled Autoantibodies Against the Insulin Receptor. Proc. Natl. Acad. Sci., U.S.A. 73: 4115-4119, 1976.